Hydroamination of olefins

Hegedus et al. have thoroughly studied the homogeneous hydroamination of olefins in the presence of transition metal complexes. However, most of these reactions are either promoted or assisted, i.e. are stoichiometric reactions of an amine with a coordinated alkene [98-101] or, if catalytic, give rise to the oxidative hydroamination products, as for example in the cyclization of o-allylanilines to 2-alkylindoles [102, 103], i.e. are relevant to Wacker-type chemistry [104]. 

Hydroamination of olefins has received considerable attention this year as a route to functionalized piperidines and spiropiperidines, particularly in regard to the investigation of new catalysts. In the synthesis of spiro-piperidines, two new mild and more general intramolecular hydroamination protocols were developed this year. One protocol uses a cationic gold-phosphine complex (Au[P(fBu)2(o-biphenyl)]Cl) as the catalyst... 

Hydroamination of olefins under most catalytic conditions proceed with Markovnikov addition of the N-H bond across the olefin. Shown below is a rhodium-catalyzed intramolecular, anti-Markovnikov, hydroamination developed for the synthesis of 3-arylpiperidines 167 <06JA6042>. Further evaluation of this reaction as a synthesis of multisubstituted piperidines revealed that substrates with substituents a or y to the amino group did not produce the expected piperidine, however, substrates with a substituent (1 to the amino group produce piperidines in high yield. 

The displacement of cyclooctene or C2H4 from an iridium(I) centre by a variety of chiral phosphines (L) leads to the formation of [ (L)IrCl 2] which, in conjunction with a source of F (phosphazenium fluoride), has been used for catalytic hydroamination of olefins. This combination leads to a 6.5 fold increase in the activity of the system and a total reversal in the enantioselectivity compared to that of the chloride analogue. There is no direct evidence of formation of a metal fluoride complex, but it is proposed that it may well form in situ and that this might explain these interesting results [75]. 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes Ifom a nitrogen nucleophile as a carbamate,a urea, an amide, or a sulfonamide. In the latter case, the reaction can be carried out intermolecularly. While the carbamates, ureas, and amides give only products of intramolecular anunations, the sulfonamides can perform the intermolecular addition. Only the addition of ureas (equation 146) takes place at room temperature, and in the rest of the additions heating is required. The catalysts of choice in all these reactions are cationic gold(I)-species stabilized by phosphines or NHC ligands. The reaction times have been reduced by the use of microwave irradiation. The mechanism of the hydroamination reaction has been studied in detail theoretically. ... 

Seayad J, Tillack A, Hartung CG, Beller M. Base-catalyzed hydroamination of olefins an environmentally friendly route to amines. Adv. Synth. Catal. 2002 344 795-813. 

To catalyze the direct hydroamination of olefins according to eq. (1) two basic approaches have been employed involving primarily the activation either of the amine or of the olefin. One possible way to activate the amine for catalysis is the transformation to the much stronger nucleophilic amide ion by deprotonation. Thus, the amides of strongly electropositive metals, such as alkali metals, alkaline earth metals, or lanthanides, are able to react with the C-C double bond under... 

Scheme 1. Catalytic cycle for the hydroamination of olefins with activation of the amine by N-H deprotonation.

Alkali metals, their hydrides, and amides have been proven as catalysts for the hydroamination of olefins under various conditions. Some typical examples for the hydroamination of ethylene as the fundamental reaction, being also of considerable industrial interest, are given in Table 2. 

Gribkov, D.V. (2005) Novel Catalysts for Stereoselective Hydroamination of Olefins Based on Rare Earth and Group IV Metals, PhD thesis, Universitat Erlangen Nurnberg. 

Besides hydrogenation, some other reactions like hydroamination of olefins as examplified in Figure 5.12 for ethylene, can be expressed by eq. (4.114) resulting in the rate equation when all the steps are irreversible (steps 1, 2, and 3 are assigned starting from the intermediate M clockwise)... 

Recently, the highly selective hydroamination of olefins with ammonia to form linear primary and secondary aliphatic amines with a new Rh/Ir catalytic system ([ Rh(cod)Cl 2, [ Ir(cod)Cl 2], aqueous TPPTS solution) has been described (Scheme 2) [14], The method is of particular importance for the production of industrially relevant, low molecular weight amines. 

Titanium-catalysed inter- and intramolecular hydroamination of olefins and allq nes is an attractive carbon-heteroatom bond-forming reaction as it is 100% atom economical (Scheme 5.5). As hydroamination reactions catalysed by early transition metals and main-group metals have been recently re-viewed, we will only cover titanium-catalysed hydroamination reactions since 2014. 

Using an interesting catalytic tethering strategy wherein simple aldehydes are employed to bring temporary intramolecularity to two reacting sites, an hydroxyl-amine and a well-positioned olefin, the synthesis of enantioenriched 1,2-diamines has been achieved by Beauchemin and co-workers [143]. By this trick, otherwise difficult to realize intermolecular hydroamination of olefins is accomplished, although at present only a few enantioselective examples have been reported (Scheme 11.55). 

Transition-Metal Catalyzed Hydroamination of Olefins and Alkynes... 

TRANSITION-METAL-CATALYZED HYDROAMINATION OF OLEFINS AND ALKYNES... 

TRANSITION-METAL-CATALYZED HYDROAMINATION OF OLEFINS AND ALKYNES Table 16.6. Effect of catalyst precursor on the intramolecular hydroamlnation In Equation 16.61. 

These intramolecular hydroaminations lead to the formation of chiral products. Thus, several studies have been devoted to developing ligands for enantioselective, intramolecular hydroaminations of olefins catalyzed by lanthanide complexes. ° Selectivities of these reactions with chiral cyclopentadienyl derivatives have been modest. Selectivities have been higher with catalysts containing non-cyclopentadienyl ligands. Some of tlie most selective catalysts are the yttrium complexes of the bis(thiolate) ligands reported by Livinghouse, the scandium and lutetium complexes of 33 -disubstituted binaphtholates reported by Hultzsch, and the BINAM-based bisamidates of Schafer.- A representative cyclization catalyzed by a member of each of these classes of catalyst are shown in Equation 16.64. 

The mechanisms of hydroaminations of olefins and alkynes are varied. Many reviews divide these mechanisms into reactions that "activate" the N-H bond or "activate" the olefin. Because each mechanism must somehow cleave both the N-H bond and the C-C Tr-bond, and the term "activate does not have a precise meaning, these mechanisms are divided in this discussion into three classes depending on the type... 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

The formation of C—N bonds is an important transformation in organic synthesis, as the amine functionality is found in numerous natural products and plays a key role in many biologically active compounds [1]. Standard catalytic methods to produce C—N bonds involve functional group manipulations, such as reductive amination of carbonyl compounds [2], addition of nucleophiles to imines [3], hydrogenation of enamides [4—8], hydroamination of olefins [9] or a C—N coupling reaction [10, 11]. Recently, the direct and selective introduction of a nitrogen atom into a C—H bond via a metal nitrene intermediate has appeared as an attractive alternative approach for the formation of C—N bonds [12-24]. 

Ruthenium and iron compounds have been claimed to catalyze the hydroamination of olefins with NH3, primary and secondary amines (120-190°C, 10-20 bar) [113, 114]. Ethylene is the most reactive olefin either with ruthenium (Eq. 4.11) or with iron catalysts (Eq. 4.12). 

Racemic NHC platinum complex (146) has been developed as a precatalyst for the intramolecular hydroamination of olefins with pending secondary alkylamine groups... 

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